U.S. patent number 8,409,167 [Application Number 11/538,950] was granted by the patent office on 2013-04-02 for devices for delivering substances through an extra-anatomic opening created in an airway.
This patent grant is currently assigned to Broncus Medical Inc. The grantee listed for this patent is Edmund J. Roschak. Invention is credited to Edmund J. Roschak.
United States Patent |
8,409,167 |
Roschak |
April 2, 2013 |
Devices for delivering substances through an extra-anatomic opening
created in an airway
Abstract
Devices and methods for delivering substances to lung tissue
through an extra-anatomic passage created in an airway.
Inventors: |
Roschak; Edmund J. (Mission
Viejo, CA) |
Applicant: |
Name |
City |
State |
Country |
Type |
Roschak; Edmund J. |
Mission Viejo |
CA |
US |
|
|
Assignee: |
Broncus Medical Inc (Mountain
View, CA)
|
Family
ID: |
39275540 |
Appl.
No.: |
11/538,950 |
Filed: |
October 5, 2006 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20080086107 A1 |
Apr 10, 2008 |
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US 20120089116 A9 |
Apr 12, 2012 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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10895022 |
Jul 19, 2004 |
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Current U.S.
Class: |
604/506;
604/500 |
Current CPC
Class: |
A61M
29/02 (20130101); A61M 31/00 (20130101); A61M
25/0082 (20130101); A61M 29/00 (20130101); A61F
2/82 (20130101); A61M 25/0068 (20130101); A61N
1/327 (20130101); A61F 2/91 (20130101); A61M
5/158 (20130101); A61M 25/10 (20130101); A61F
2230/005 (20130101); A61F 2210/0076 (20130101); A61F
2230/0078 (20130101); A61M 2025/1081 (20130101); A61F
2220/0075 (20130101); A61B 2017/00809 (20130101) |
Current International
Class: |
A61M
31/00 (20060101) |
Field of
Search: |
;604/500,506,507,508,510 |
References Cited
[Referenced By]
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placement and influence of topical mitomycin Con stent patency," J.
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Primary Examiner: Mehta; Bhisma
Attorney, Agent or Firm: Levine Bagade Han LLP
Parent Case Text
CROSS REFERENCE TO RELATED APPLICATIONS
This is a continuation-in-part of U.S. patent application Ser. No.
10/895,022 filed Jul. 19, 2004 now abandoned, publication No. US
2005/0137611 A1.
Claims
I claim:
1. A method of treating diseased lung tissue in a lung, the method
comprising: advancing a delivery catheter through a natural
respiratory opening and into the lung; creating and maintaining an
extra-anatomic opening in an airway wall at a target site such that
patency of the extra-anatomic opening is artificially extended
beyond a natural healing response; and delivering a substance
through the extra-anatomic opening to treat a region of diseased
tissue beyond the airway wall in the lung.
2. The method of claim 1, further comprising: identifying the
region of diseased tissue prior to delivering the substance; and
selecting the target site.
3. The method of claim 2, where identifying the region in the lung
having diseased tissue comprises locating a tumor in the lung.
4. The method of claim 3, further comprising delivering the
substance through the extra-anatomic opening to treat the
tumor.
5. The method of claim 2, where identifying the region in the lung
having diseased tissue comprises locating a region of trapped
gasses.
6. The method of claim 5, further comprising delivering the
substance through the extra-anatomic opening to collapse the region
of the lung containing the collapsed gasses.
7. The method of claim 2, where identifying the region in the lung
having diseased tissue comprises locating the region using an
imaging method selected from radiography, computer tomography,
ultrasound, Doppler, MRI, PET and acoustic imaging.
8. The method of claim 2, where selecting the target site comprises
scanning for the presence of a blood vessel in the airway wall to
avoid puncturing the blood vessel during creation of the
extra-anatomic opening.
9. The method of claim 8, where scanning the target site comprises
using a modality selected from the group consisting of visual
inspection, x-ray, ultrasound, Doppler, acoustic, MRI, PET, and
computed tomography (CT) scans.
10. The method of claim 1, further comprising inserting an implant
within the extra-anatomic opening.
11. The method of claim 10, further comprising removing the implant
subsequently to delivering the substance.
12. The method of claim 1, wherein creating the extra-anatomic
opening comprises using a needle-like member which punctures the
tissue to create the extra-anatomic opening.
13. The method of claim 12, where the needle-like member delivers
the substance.
14. The method of claim 1, where the substance comprises a
substance selected from the group consisting of antimetabolites,
antithrobotics, anticoagulants, antiplatelet agents,
thorombolytics, antiproliferatives, anti-inflammatories, agents
that inhibit hyperplasia, agents that inhibit restenosis, smooth
muscle cell inhibitors, growth factors, growth factor inhibitors,
cell adhesion inhibitors, cell adhesion promoters and a combination
thereof.
15. The method of claim 1, where the substance comprises a
substance selected from the group consisting of analgesics,
anticonvulsives, antibiotics, antimicrobials, antineoplastics,
Histamine 2 antagonists, steroids, non-steroidal
anti-inflammatories, hormones, immunomodulators, mast cell
stabilizers, nucleoside analogues, respiratory agents,
antihypertensives, antihistamines, ACE inhibitors, cell growth
factors, nerve growth factors, anti-angiogenic agents or
angiogenesis inhibitors, tissue irritants, a compound comprising
talc, poisons, cytotoxic agents, silver, aluminum, zinc, platinum,
arsenic, epithelial growth factors, pyrolitic carbon,
titanium-nitride-oxide, taxanes, fibrinogen, collagen, thrombin,
phosphorylcholine, heparin, rapamycin, radioactive 188Re and 32P,
silver nitrate, dactinomycin, sirolimus, everolimus, Abt-578,
tacrolimus, camptothecin, etoposide, vincristine, mitomycin,
fluorouracil, or cell adhesion peptides, and a combination
thereof.
16. The method of claim 1, where maintaining the extra anatomic
opening occurs by an act selected from the group consisting of
applying a bio-active substance and implanting a conduit.
17. A method for locating and treating cancerous tissue in a lung
comprising: advancing a device through an oral opening and into an
airway within the lung; locating a target site along an airway
wall, the target site being in the vicinity of the cancerous
tissue; and delivering a substance through an existing surgically
created opening to treat the cancerous tissue beyond the airway
wall in the lung where the existing surgically created opening was
previously created such that patency of the surgically created
opening is extended beyond at least creation of the surgically
created opening.
18. The method of claim 17, further comprising sensing for a blood
vessel prior to said delivering step.
19. The method of claim 17, further comprising preventing closure
of the surgical opening wherein said preventing step is performed
using a combination of mechanical and biochemical means.
20. The method of claim 19 where said delivering step comprises
inserting an instrument through the surgical opening and injecting
said substance from said instrument to the tissue.
21. The method of claim 17 where the tissue is a tumor.
22. The method of claim 17, where previously creating the existing
surgically created opening included an act selected from the group
consisting of applying a bio-active substance; dilating; piercing,
and implanting a conduit.
Description
FIELD OF THE INVENTION
This is directed to methods and devices for treating lungs. The
methods and devices create channels, also known as extra-anatomic
openings, in airways. Maintaining the patency of the channels
allows air to pass directly out of the lung tissue which
facilitates the exchange of oxygen ultimately into the blood and/or
decompresses hyper-inflated lungs. In an additional variation, the
channels provide access points for improved targeted delivery of
medications or other substances to parenchymal lung tissue.
BACKGROUND OF THE INVENTION
It was found that creation of collateral channels in chronic
obstructive pulmonary disease (COPD) patients allowed expired air
to pass out of the lungs and decompressed hyper-inflated lungs.
Such methods and devices for creating and maintaining collateral
channels are discussed in U.S. patent application Ser. No.
09/633,651, filed on Aug. 7, 2000; U.S. patent application Ser.
Nos. 09/947,144, 09/946,706, and 09/947,126 all filed on Sep. 4,
2001; U.S. Provisional Application No. 60/317,338 filed on Sep. 4,
2001; U.S. Provisional Application No. 60/334,642 filed on Nov. 29,
2001; U.S. Provisional Application No. 60/367,436 filed on Mar. 20,
2002; and U.S. Provisional Application No. 60/374,022 filed on Apr.
19, 2002 each of which is incorporated by reference herein in its
entirety.
The creation of these collateral channels or extra-anatomic
openings also provide convenient access points to the lung
parenchyma for delivery of substances to treat diseased tissue that
may reside within the lung. The use of such openings allows for
treatment in a minimally invasive manner and efficiently delivering
needed substances to the desired area.
SUMMARY OF THE INVENTION
The invention includes methods and devices for treating a lung. The
method includes treating diseased lung tissue by identifying a
region in a lung having the diseased lung tissue, selecting a
target site at an airway wall, creating an extra-anatomic opening
at the target site; and delivering a substance through the
extra-anatomic opening to treat the diseased tissue. In most cases,
the diseased tissue is present beyond the wall of the airway and in
the parenchymal tissue of the lung.
As discussed herein the method may or may not include placement of
an implant. For example, the substance may or may not be delivered
through the implant. Moreover, the conduit may be subsequently
removed from the airway after the diseased tissue is sufficiently
treated. The treatment may treat regions of destroyed tissue and
trapped gasses by inducing a collapse of the tissue. Alternatively,
or in combination, the treatment may be directed towards tumors or
other conditions of the lung.
The methods relating to identifying regions of tissue, selecting a
target site, avoidance of blood vessels, and creation of the
extra-anatomic opening may rely on the teachings discussed herein
that are suited to creation of a collateral opening for releasing
trapped gasses.
The substance may be delivered using any catheter capable of being
deployed in the lungs. The method may include advancing a delivery
catheter into the lungs to deliver the substance. Alternatively, or
in combination, the substance may be delivered using the devices
described below.
The method also includes identifying the areas of the diseased
tissue using the modes described herein or other modes that are
suited for the particular medical condition in question. For
example, a site for treating a tumor may be located using such
means that are well suited for tumor identification.
Turning now to the methods and devices for selecting sites and
creating openings, in one variation, the invention includes a
method comprising selecting a treatment site in an airway of the
lung, creating a hole in an airway wall of the airway; and
expanding the hole in the airway wall.
Selecting the treatment site may include visual inspection of the
site or inspection for the presence or absence of a blood vessel
underneath the surface of the airway wall.
Selection of the site may be performed or aided by non-invasive
imaging. Such imaging may include visual inspection, x-ray,
ultrasound, Doppler, acoustic, MRI, PET, and computed tomography
(CT) scans. Furthermore, a substance may be administered into the
lungs to assist in the selection of the treatment site. For
example, the substance may comprise a hyperpolarized gas, a
thermochromatic dye, a regular dye, and/or a contrast agent.
Variations of the invention include the use of a less-traumatic
holemaker for creation of the channel (note that a channel includes
a hole that is created and subsequently expanded.) The less
traumatic holemaker may include a piercing member (e.g., a needle,
a cannula, a blade, a tube, a rod or other similar structure). The
less traumatic holemaker may also include devices which minimize
the collateral damage to tissue (e.g., low temperature RF devices,
pulsating RF, low temperature laser, ultrasound, high pressure
water, etc.)
In particular, the devices and methods prevent closure of the
channel such that air may flow through the channel and into the
airway. Such channels may be made by a variety of methods as
discussed in the patents incorporated by reference above. For
example, the channel may be made via a surgical incision, a needle,
a rotary coring device, etc. Furthermore, the channel may be made
by an energy based device, e.g., RF device, laser, etc. However, it
has been noted that use of low temperature devices, e.g.,
mechanical devices, to create the channel result in less trauma to
surrounding tissue and thereby minimize the healing response of the
tissue. Accordingly, such modes of creating the channel often
result in less occlusion of the channel.
The method includes expanding the hole by inserting a conduit into
the hole. Furthermore, the method may comprise partially expanding
the hole by deploying the conduit in the hole, and then fully
expanding the hole by expanding the conduit within the hole.
Preventing closure may be performed using various approaches
including, but not limited to, biochemical, electrical, thermal,
irradiation, or mechanical approaches (or any combination
thereof).
The method may also include delivering a bio-active composition, as
described herein, to maintain patency of the channel or conduit.
The bio-active composition may be delivered to the airway wall
prior to creation of the channel, subsequent to creation of the
channel, and/or after insertion and deployment of the conduit. The
bio-active composition may also be delivered through a drug eluting
process, either through a composition placed on the conduit, or via
delivery of a separate eluting substance.
Biochemical approaches include delivery of medicines that inhibit
closure of the surgically created channel. The medicines may be
delivered locally or systematically. In one variation, a delivery
catheter includes a dispense lumen that sends a drug to the target
site. Also, bioactive substances may be delivered to the channel
tissue using various delivery vehicles such as a conduit. The
bioactive substance may be disposed on an exterior surface of the
conduit such that it interacts with the channel tissue when the
conduit is placed at the injury site. Also, bioactive substances
may be delivered to the channel tissue before or after the conduit
is positioned in the channel. The bioactive agent may also be
delivered to the target site alone. That is, a medicine may be sent
to the surgically created channel as the sole mechanism for
maintaining the patency of the channel.
Also, systematic delivery of medicines may be carried out through
digestion, injection, inhalation, etc. Systematic delivery of
medicines may be provided alone or in combination with other
techniques described herein. For example, a patient having
undergone the procedures described herein may be prescribed
steroids and/or COX-2 inhibitors in an attempt to prolong the
effects of the treatment.
Any of the conduits discussed herein may also include at least one
visualization feature disposed on a portion of the tissue barrier.
The visualization feature may be a stripe circumferentially
disposed about at least a portion of the center section. The
visualization feature serves to aid in placement or deployment of
the conduit in a target site.
Another conduit for maintaining the patency of a channel created in
tissue comprises a radially expandable center section and extension
members as described above. A bioactive substance is disposed on at
least a portion of a surface of the conduit. Also, when the conduit
is radially expanded it has an overall length and an inner diameter
such that a ratio of the overall length to the inner diameter
ranges from 1/6 to 2/1. The conduit may also be provided such that
this ratio ranges from 1/4 to 1/1 and perhaps, 1/4 to 1/2. A tissue
barrier may be disposed on at least a portion of the exterior
surface corresponding to the center section. The tissue barrier may
be comprised of various materials including but not limited to
polymers and elastomers. An example of a material which may be used
for the tissue barrier is silicone. Additional matrixes of
biodegradable polymer and medicines may be associated with the
tissue barrier such that controlled doses of medicines are
delivered to the tissue opening.
The invention includes a hole-making catheter for creating and
dilating an opening within tissue, the catheter comprising an
elongate shaft having a proximal portion and a distal portion, and
at least one lumen extending through the proximal end; a balloon
having an interior in fluid communication with the lumen, the
balloon located on the distal portion of the elongate shaft, the
balloon having an uninflated state and an inflated state; a
piercing member located at the distal portion of the elongate
shaft, the piercing member being extendable and retractable within
the elongate shaft; and a depth limiter stop located on the
exterior of the distal portion of the elongate shaft, proximal to
the balloon and larger in working diameter than the uninflated
balloon, which limits the maximum penetration of the catheter into
tissue.
The piercing member may include a body portion having a lumen
extending therethrough. The lumen of the piercing member may be in
fluid communication with a central lumen of the elongate shaft. In
some variations of the invention an obturator is used within the
device, where the obturator is slidably located within the lumen of
the elongate body and piercing member.
The elongate body and/or piercing member may have multiple lumens.
For example, they may be constructed from multi-lumen tubing. In
some variations, the piercing member is retractable within the
elongate shaft.
The balloon member may consist of a distensible balloon or a
non-distendsible balloon. For either type of balloon, the working
diameter may closely match the outer diameter of the piercing
member.
The invention may also include an implant located about the balloon
of the device. In use, the piercing member would create a channel
within the tissue, the device is then further advanced until the
implant is located within the channel. Inflation of the balloon
then deploys the implant within the channel thereby improving the
patency of the channel.
Implants for the present invention include, but are not limited to,
a stent, conduit, grommet, valve, graft, anchor, etc.
It should be noted that since the device must often access airways
deep within the lung, the elongate shaft may be comprised of a
flexible material. In particular, the elongate shaft may be
sufficiently flexible to pass through a fully articulated
bronchoscope.
The piercing member of the current invention may also be used to
deliver bio-active agents to the site of the collateral channel. As
described herein, such agents may increase the duration of patency
of the channels and/or implants.
The invention includes a balloon catheter for deploying a device
within an opening in tissue, the balloon catheter comprising an
elongate shaft having a proximal portion, a distal portion, a
proximal end, a distal end; and at least one lumen extending
through the proximal end, a balloon having an interior in fluid
communication with the lumen, the balloon located on the distal end
portion of the elongate shaft, a guide member extending distally
from the distal end of the elongate shaft, the guide member
comprising a rounded surface at an end opposite to the elongate
shaft, where the guide member has sufficient column strength to
penetrate the opening in tissue, the guide member further
comprising at least one resistance surface a such that when the
body enters the opening, the resistance surface exerts resistance
against tissue upon removal of the guide member from the
opening.
The resistance surface may have an increased diameter greater to
provide resistance upon removal from tissue. It may alternatively,
or in combination, comprise a rough surface to provide added
friction upon removal of the device.
The guide member may be tapered, rounded, partially-spherical,
elliptical, prolate, cone-shaped, triangular, or any similar shape.
It is contemplated that there may be more than one resistance
surface on the guide body. Moreover, the guide body may have a
wavy/variable diameter shape providing several resistance surfaces
on the areas of increased diameter.
The device may also be used with an implant that may be located
about the balloon where upon expansion of the balloon, the implant
deploys. The implant may be selected from a stent, conduit,
grommet, valve, graft, and anchor.
In another variation of the invention, the balloon catheter may
further comprise a dilating member located distally of the balloon.
The dilating member may be is located on the distal portion of the
shaft between the distal end and the balloon and may comprise a
tapered section, a second balloon, or other similar structure.
In some variations of the invention, the dilating member may be
retractable within the elongate shaft.
The device may also include a needle assembly moveably located in
the instrument lumen, where the needle assembly is advanceable
through a hole-making lumen and out of the opening in the rounded
surface.
The balloon catheter may be constructed to be sufficient
flexibility to advance through a fully articulated
bronchoscope.
The balloon catheter may also be configured to deliver bio-active
substances (e.g., drugs, medicines, compounds, etc.) to the tissue,
either via the elongate tube or the guide member. Furthermore, the
device may be adapted to provide suction to clear the target
site.
The invention includes a hole-making catheter for creating and
dilating an opening within tissue, the catheter comprising; an
elongate shaft having a proximal portion and a distal portion, and
at least one lumen extending through the proximal end; a
nondistensible balloon having an interior in fluid communication
with the lumen, the nondistensible balloon located on the distal
portion of the elongate shaft; and a piercing member located at the
distal portion of the elongate shaft, the piercing member being
extendable and retractable within the elongate shaft.
The invention includes an implant delivery system for deploying the
implant within a wall of tissue, the system comprising; an elongate
shaft having a distal portion, a proximal end, a distal end, at
least one lumen extending through the proximal end; a balloon
member having an interior in fluid communication with the lumen,
the balloon member located on the distal portion of the elongate
shaft; a piercing member distally located to the distal end of the
elongate shaft within the second lumen, the solid piercing member
having a sharpened distal end adapted to penetrate tissue; and an
expandable implant located about the balloon member.
The preceding illustrations are examples of the invention described
herein. It is contemplated that, where possible, combinations of
features/aspects of specific embodiments or combinations of the
specific embodiments themselves are within the scope of this
disclosure.
This application is also related to the following application
60/420,440 filed Oct. 21, 2002; 60/387,163 filed Jun. 7, 2002; Ser.
No. 10/235,240 filed Sep. 4, 2002; Ser. No. 09/947,144 filed Sep.
4, 2001; Ser. No. 09/908,177 filed Jul. 18, 2001; Ser. No.
09/633,651 filed Aug. 7, 2000; and 60/176,141 filed Jan. 14, 2000;
Ser. No. 10/080,344 filed Feb. 21, 2002; Ser. No. 10/079,605 filed
Feb. 21, 2002; Ser. No. 10/280,851 filed Oct. 25, 2002; and Ser.
No. 10/458,085 filed Jun. 9, 2003. Each of which is incorporated by
reference herein.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1A-1C illustrate various states of the natural airways and
the blood-gas interface.
FIG. 1D illustrates a schematic of a lung demonstrating a principle
of the invention described herein.
FIG. 2A illustrates a side view of a conduit in an undeployed
state.
FIG. 2B illustrates a side view of the conduit of FIG. 2A shown in
a deployed shape.
FIG. 2C illustrates a front view of the conduit shown in FIG.
2B.
FIG. 2D is a cylindrical projection of the undeployed conduit shown
in FIG. 2A.
FIG. 2E illustrates a side view of another variation of a conduit
in an undeployed shape.
FIG. 2F illustrates a side view of the conduit of FIG. 2E in a
deployed state.
FIG. 2G is a cylindrical projection of the undeployed conduit shown
in FIG. 2E.
FIG. 3A illustrates a side view of a conduit having a tissue
barrier in a deployed state.
FIG. 3B illustrates a side view of a conduit having a tissue
barrier.
FIG. 3C is a front view of the conduit shown in FIG. 3B.
FIG. 3D illustrates a conduit positioned in a channel created in a
tissue wall.
FIG. 3E is a cross sectional view of the conduit shown in FIG. 3B
taken along line 3E-3E.
FIGS. 3F-3G depict another conduit including a membrane that
supports a bioactive substance; the bioactive substance may be
coated on the membrane.
FIGS. 4A-4C a variation of selecting a site, creating a channel at
the site using a less traumatic hole-maker, and expanding the
channel.
FIGS. 4D-4K illustrate variations of piercing members for creating
collateral channels.
FIGS. 5A-5C illustrate a method for deploying a conduit.
FIGS. 5D-5E illustrate a method for deploying a conduit within
another implant.
FIGS. 6A-6B illustrate a method for deploying a conduit at an
angle.
FIGS. 7A-7B illustrate placement of a conduit within a channel by
using a guide member.
FIGS. 8A-8F illustrate additional variations of guide bodies for
use with catheters of the present invention.
FIGS. 9A-9B illustrate additional features for use with guide
bodies of the present invention.
FIGS. 10A-10B respectively illustrate delivery of substances
through an opening in the airway and through a conduit placed
within the opening.
DETAILED DESCRIPTION OF THE INVENTION
Described herein are devices (and methods) for treating diseased
lung tissue. In particular, methods and devices are described that
serve to maintain collateral openings or channels through an airway
wall so that air is able to pass directly out of the lung tissue
and into the airways or so that substances may be delivered to
parenchymal tissue beyond the airways but within the lungs.
By "channel" it is meant to include, but not be limited to, any
opening, hole, slit, channel or passage created in the tissue wall
(e.g., airway wall). The channel may be created in tissue having a
discrete wall thickness and the channel may extend all the way
through the wall. Also, a channel may extend through lung tissue
which does not have well defined boundaries such as, for example,
parenchymal tissue.
The channels may be maintained by preventing or inhibiting tissue
from growing into or otherwise blocking the channel. Chemical,
electrical, light, mechanical, or a combination of any two or more
of these approaches may be performed to maintain the channel
openings. For example, the channel walls may be treated with a
bioactive agent which inhibits tissue growth. The bioactive agent
may be delivered locally or systematically. Also, the channels may
be treated with rf energy, heat, electrical energy, or radiation to
inhibit tissue overgrowth. These treatments may be performed once,
periodically, or in response to the severity of the channel
blockage. For example, the tissue blockage may be periodically
removed with a laser or another tissue-removal tool. Also,
mechanical devices and instruments may be deployed in the channel
to prevent tissue growth from blocking the channel. Mechanical
devices include without limitation conduits, valves, sponges, etc.
These mechanical devices may be deployed permanently or
temporarily. If deployed temporarily, the devices are preferably
left in the channel for a sufficient amount of time such that the
channel tissue heals coaxially around the device if the medical
practitioner intends to create a permanent opening in the airway
wall.
FIGS. 1A-1C are simplified illustrations of various states of a
natural airway and a blood gas interface found at a distal end of
those airways. FIG. 1A shows a natural airway 100 which eventually
branches to a blood gas interface 102.
Although not shown, the airway comprises an internal layer of
epithelial pseudostratified columnar or cuboidal cells. Mucous
secreting goblet cells are also found in this layer and cilia may
be present on the free surface of the epithelial lining of the
upper respiratory airways. Supporting the epithelium is a loose
fibrous, glandular, vascular lamina propria including mobile
fibroblasts. Deep in this connective tissue layer is supportive
cartilage for the bronchi and smooth muscle for the bronchi and
bronchioles.
FIG. 1B illustrates an airway 100 and blood gas interface 102 in an
individual having COPD. The obstructions 104 impair the passage of
gas between the airways 100 and the interface 102. FIG. 1C
illustrates a portion of an emphysematous lung where the blood gas
interface 102 expands due to the loss of the interface walls 106
which have deteriorated due to a biochemical breakdown of the walls
106. Also depicted is a constriction 108 of the airway 100. It is
generally understood that there is usually a combination of the
phenomena depicted in FIGS. 1A-1C. Often, the states of the lung
depicted in FIGS. 1B and 1C may be found in the same lung.
FIG. 1D illustrates airflow in a lung 118 when conduits 200 are
placed in collateral channels 112. As shown, collateral channels
112 (located in an airway wall) place lung tissue 116 in fluid
communication with airways 100 allowing air to pass directly out of
the airways 100 whereas constricted airways 108 may ordinarily
prevent air from exiting the lung tissue 116. While the invention
is not limited to the number of collateral channels which may be
created, it is to be understood that 1 or 2 channels may be placed
per lobe of the lung and perhaps, 2-12 channels per individual
patient. However, as stated above, the invention includes the
creation of any number of collateral channels in the lung. This
number may vary on a case by case basis. For instance, in some
cases in an emphysematous lung, it may be desirable to place 3 or
more collateral channels in one or more lobes of the lung.
Although FIG. 1D depicts a mechanical approach to maintaining
channels in the airway walls, the channel openings may be
maintained using a variety of approaches or combinations of
approaches.
As shown in FIGS. 2A-2G, the conduits described herein generally
include a center section 208 and at least one extension member (or
finger) 202 extending from each end of the center section. The
extension members, as will be discussed in more detail below, are
capable of deflecting or outwardly bending to secure the conduit in
an opening created in an airway wall thereby maintaining the
patency of the opening. The extension members may deflect such that
opposing extension members may form a V, U or other type of shape
when viewed from the side.
Additionally, the conduits shown in FIGS. 2A-2G include a
center-control segment 235, 256 which restricts or limits radial
expansion of the center section. The center-control segments are
adapted to straighten as the center section is radially expanded.
Once the center-control segments become straight or nearly
straight, radial expansion of the conduit is prevented. In this
manner, the radial expansion of the conduit may be self
controlled.
It is understood that the conduits discussed herein are not limited
to those shown in the figures. Instead, conduits of various
configurations may be used as described herein. Such conduits are
described in the following patent application Ser. No. 09/908,177
filed Jul. 18, 2001; PCT/US03/12323 filed Apr. 21, 2003; Ser. No.
09/947,144 filed Sep. 4, 2001; Ser. No. 10/235,240 filed Sep. 4,
2002; and Ser. No. 10/458,085 filed Jun. 9, 2003 the entirety of
each of which is hereby incorporated by reference.
Conduit States
The conduits described herein may have various states
(configurations or profiles) including but not limited to (1.) an
undeployed state and (2.) a deployed state.
The undeployed state is the configuration of the conduit when it is
not secured in an opening in an airway wall and, in particular,
when its extension members (or fingers) are not outwardly deflected
to engage the airway wall. FIG. 2A is a side view of a conduit 200
in an undeployed state. As shown in this figure, extension members
202A, 202B extend straight from the ends 210, 212 respectively of
center section 208. The extension members shown in this example are
parallel. However, the invention is not so limited and the
extension members need not be parallel.
The deployed state is the configuration of the conduit when it is
secured in a channel created in an airway wall and, in particular,
when its extension members are outwardly bent to engage the airway
wall such that the conduit is fixed in the opening. An example of a
conduit in its deployed configuration is shown in FIGS. 2B and 2C.
FIG. 2B is a side view of a conduit in its deployed state and FIG.
2C shows a front view of the conduit of FIG. 2B.
Center Section of the Conduit
As shown in FIGS. 2A-2D, the conduit includes a center section 208
having a short passageway. This center section may be a
tubular-shaped open-frame (or mesh) structure having a plurality of
ribs. Also, as explained in more detail below, the center section
may be a sheet of material.
The axial length of the center section or passageway may be
relatively short. In FIGS. 2A-2D, the passageway's length is about
equal to the width of a wire segment or rib. Here, the center
section serves as a bridge or junction for the extension members
and it is not required to be long. The axial length of the
passageway may therefore be less than 1 mm and even approach 0 mm.
In one example, the length of the center section is less than twice
the square root of a cross sectional area of the center section.
However, the center section may also have passageways which have
lengths greater than 1 mm.
The overall length (L) of the conduit may be distinguished from the
length of the center section because the overall length includes
the lengths of the extension members. Further, the overall length
(L) is dependent on which state the conduit is in. The overall
length of the conduit will typically be shorter when it is in a
deployed state as shown in FIG. 2B than when it is in an undeployed
state as shown in FIG. 2A. The overall length (L) for a deployed
conduit may be less than 6 mm and perhaps, between 1 and 20 mm.
FIG. 2C shows a front view of the conduit 200 shown in FIG. 2B.
FIG. 2C shows the passageway having a hexagonal (or circular) cross
section. The cross-section, however, is not so limited. The cross
section may be circular, oval, rectangular, elliptical, or any
other multi-faceted or curved shape. The inner diameter (D.sub.1)
of the center section, when deployed, may range from 1 to 10 mm and
perhaps, from 2 to 5 mm. Moreover, in some variations, the
cross-sectional area of the passageway, when deployed, may be
between 0.2 mm.sup.2 to 300 mm.sup.2 and perhaps between 3 mm.sup.2
and 20 mm.sup.2
The diameter of the center section, when deployed, thus may be
significantly larger than the passageway's axial length (e.g., a 3
mm diameter and an axial length of less than 1 mm). This ratio of
the center section length to diameter (D1) may range from about
0:10 to 10:1, 0.1:6 to 2:1 and perhaps from 1:2 to 1:1.
The diameter of the center section, when deployed, may also be
nearly equal to the overall length (L) of the conduit 200. This
overall length (L) to diameter (D1) ratio may range from 1:10 to
10:1, 1:6 to 2:1, and perhaps from 1:4 to 1:1. However, the
invention is not limited to any particular dimensions or ratio
unless so indicated in the appended claims. Rather, the conduit
should have a center section such that it can maintain the patency
of a collateral channel in an airway wall. The dimensions of the
center section (and the conduit as a whole) may be chosen based on
the tissue dimensions. When the channel is long in its axial
length, for example, the length of the center section may likewise
be long or identical to the channel's length.
Extension Members of the Conduit
As mentioned above, extending from the ends of the center section
208 are extension members 202A, 202B which, when the conduit is
deployed, form angles A1, A2 with a central axis of the passageway.
When viewed from the side such as in FIG. 2B, opposing extension
members may have a V, U, or other shape. The extension members
202A, 202B may thus outwardly rotate until they sandwich tissue
(not shown) between opposing extension members.
The angles A1, A2 may vary and may range from, for example, 30 to
150 degrees, 45 to 135 degrees and perhaps from 30 to 90 degrees.
Opposing extension members may thus form angles A1 and A2 of less
than 90 degrees when the conduit is deployed in a channel. For
example, angles A1 and A2 may range from 30 to 60 degrees when the
conduit is deployed.
The conduits of the present invention are effective and may
maintain a surgically created opening despite not substantially
sandwiching tissue between opposing extension members as described
above. Additionally, it is not necessary for the conduits of the
present invention to prevent air from flowing along the exterior of
the conduit. That is, air may move into (and through) spaces
between the exterior of the conduit and the interior wall of the
tissue channel. Thus, fluidly sealing the edges of the conduit to
prevent side flow or leakage around the conduit is not crucial for
the conduits to be effective. However, the conduits of the present
invention are not so limited and may reduce or eliminate side flow
by, for example, increasing the angles A1 and A2 and adding sealant
around the exterior of the conduit.
Moreover, the angle A1 may be different than angle A2. Accordingly,
the conduit may include proximal extension members which are
parallel (or not parallel) to the distal extension members.
Additionally, the angle corresponding to each proximal extension
member may be different or identical to that of another proximal
extension member. Likewise, the angle corresponding to each distal
extension member may be different or identical to that of another
distal extension member.
The extension members may have a length between 1 and 20 mm and
perhaps, between 2 and 6 mm. Also, with reference to FIG. 2C, the
outer diameter (D.sub.2) of a circle formed by the free ends of the
extension members may range from 2 to 20 and perhaps, 3 to 10 mm.
However, the invention is not limited to the dimensions disclosed
above. Furthermore, the length of the distal extension members may
be different than the length of the proximal extension members. The
length of the distal extension members may be, for example, longer
than that of the proximal extension members. Also, the lengths of
each proximal extension member may be different or identical to
that of the other proximal extension members. Likewise, the lengths
of each distal extension member may be different or identical to
that of the other distal extension members.
The number of extension members on each end of the center section
may also vary. The number of extension members on each end may
range from 2-10 and perhaps, 3-6. Also, the number of proximal
extension members may differ from the number of distal extension
members for a particular conduit. Moreover, the extension members
may be symmetrical or non-symmetrical about the center section. The
proximal and distal extension members may also be arranged in an
in-line pattern or an alternating pattern. The extension members or
the center section may also contain barbs or other similar
configurations to increase adhesion between the conduit and the
tissue. The extension members may also have openings to permit
tissue ingrowth for improved retention.
The shape of the extension members may also vary. They may be
open-framed and somewhat petal-shaped as shown in FIGS. 2A-2D. In
these figures, the extension members 202A, 202B comprise wire
segments or ribs that define openings or spaces between the
members. However, the invention is not so limited and the extension
members may have other shapes. The extension members may, for
example, be solid or they may be filled.
In another variation the conduit is constructed to have a delivery
state. The delivery state is the configuration of the conduit when
it is being delivered through a working channel of a bronchoscope,
endoscope, airway or other delivery tool. The maximum outer
diameter of the conduit in its delivery state must therefore be
such that it may fit within the delivery tool, instrument, or
airway.
In one variation, the conduit is radially expandable such that it
may be delivered in a smaller working channel of a scope while
maximizing the diameter to which the conduit may expand upon
deployment. For example, sizing a conduit for insertion into a
bronchoscope having a 2 mm or larger working channel may be
desirable. Upon deployment, the conduit may be expanded to have an
increased internal diameter (e.g., 3 mm.) However, the invention is
not limited to such dimensions. It is contemplated that the
conduits 200 may have center sections that are expanded into a
larger profile from a reduced profile, or, the center sections may
be restrained in a reduced profile, and upon release of the
restraint, return to an expanded profile.
Additionally, the conduit need not have a smaller delivery state.
In variations where the center section is not able to assume a
second smaller delivery profile, a maximum diameter of the first or
deployed profile will be sufficiently small such that the conduit
may be placed and advanced within an airway or a working channel of
a bronchoscope or endoscope. Also, in cases where the conduit is
self-expanding, the deployed shape may be identical to the shape of
the conduit when the conduit is at rest or when it is completely
unrestrained.
Additionally the conduit may be partially expanded in its proximal
region in the delivery state, as shown in figure X. The partially
expanded portion would still me sized small enough to fit within
the working channel of the bronchoscope, but would be significantly
larger (e.g., 0.5-2 mm) larger that the distal portion of the
conduit. This partial expansion allows for easy placement of the
conduit by providing a physical stop for the conduit within the
airway wall. After the conduit is placed the entire conduit can be
expanded to its intended expanded shape.
The partial expansion state can also be achieved by partially
inflating the proximal section of the conduit with a separate
balloon on the delivery device. Another possible method is to
design the conduit to preferentially expand the proximal section
before the distal section, thereby partially expanding the conduit
to create the size differential, placing the stent inside the
airway wall with the aid of the stop, and then fully expanding the
conduit.
Control Members
The conduit 200 shown in FIGS. 2A-2D also includes
diametric-control segments, tethers, or leashes 235 to control and
limit the expansion of the center section 208 when deployed. This
center-control segment 235 typically is shaped such that when the
conduit radially expands, the center-control segment bends until it
is substantially straight or no longer slack. Such a center-control
segment 235 may be circular or annular shaped. However, its shape
may vary widely and it may have, for example, an arcuate,
semi-circular, V, or other type of shape which limits the expansion
of the conduit.
Typically, one end of the center-control segment is attached or
joined to the center section at one location (e.g., a first rib)
and the other end of the center-control segment is connected to the
center section at a second location (e.g., a rib adjacent or
opposite to the first rib). However, the center-control segments
may have other constructs. For example, the center-control segments
may connect adjacent or non-adjacent center section members.
Further, each center-control segment may connect one or more ribs
together. The center-control segments may further be doubled up or
reinforced with ancillary control segments to provide added control
over the expansion of the center section. The ancillary control
segments may be different or identical to the primary control
segments.
FIG. 2B illustrates the conduit 200 in its deployed configuration.
As discussed above, the center-control segments 235 may bend or
otherwise deform until they maximize their length (i.e., become
substantially straight) such as the center-control segments 235
shown in FIG. 2B. However, as discussed above, the invention is not
so limited and other types of center-control segments may be
employed.
As shown in FIGS. 2E-2G, control segments 252 may also be used to
join and limit the expansion of the extension members 254 or the
control segments may be placed elsewhere on the conduit to limit
movement of certain features to a maximum dimension. By controlling
the length of the control segments, the shape of the deployed
conduit may be controlled. In the conduit shown in FIGS. 2E-2G, the
conduit includes both center-control segments 256 and distal
control segments 252. The center-control segments are arcuate
shaped and join adjacent rib sections of the center section and the
distal-control segments are arcuate and join adjacent distal
extension members.
FIG. 2F illustrates the conduit in a deployed configuration and
shows the various control members straightening as the extension
members and center section deploy. The proximal extension members,
however, are not restricted by a control member and consequently
may be deflected to a greater degree than the distal extension
members. Accordingly, a conduit having control members connecting,
for example, regions of the center section and having additional
control segments connecting extension members, may precisely limit
the maximum profile of a conduit when it is deployed. This is
desirable where overexpansion of the conduit is hazardous.
This also serves to control the deployed shape of the conduit by,
for instance, forcing angle A1 to differ from angle A2. Using
control segments in this manner can provide for cone-shaped
conduits if the various types of control-segments have different
lengths. For example, providing longer proximal-control segments
than distal-control segments can make angle A1 larger than angle
A2. Additionally, cylindrical-shaped conduits may be provided if
the center-control segments and the extension-control segments are
sized similarly such that angle A1 equals angle A2. Again, the
control segments straighten as the conduit expands and the conduit
is thus prevented from expanding past a predetermined amount.
The control segments, as with other components of the conduit, may
be added or mounted to the center section or alternatively, they
may be integral with the center section. That is, the control
segments may be part of the conduit rather than separately joined
to the conduit with adhesives or welding, for example. The control
segments may also be mounted exteriorly or interiorly to the
members to be linked. Additionally, sections of the conduit may be
removed to allow areas of the conduit to deform more readily. These
weakened areas provide another approach to control the final shape
of the deployed conduit. Details for creating and utilizing
weakened sections to control the final shape of the deployed
conduit may be found in U.S. patent Ser. No. 09/947,144 filed on
Sep. 4, 2001.
Manufacture and Materials
The conduit described herein may be manufactured by a variety of
manufacturing processes including but not limited to laser cutting,
chemical etching, punching, stamping, etc. For example, the conduit
may be formed from a tube that is slit to form extension members
and a center section between the members. One variation of the
conduit may be constructed from a metal tube, such as stainless
steel, 316L stainless steel, titanium, titanium alloy, nitinol,
MP35N (a nickel-cobalt-chromium-molybdenum alloy), etc. Also, the
conduit may be formed from a rigid or elastomeric material that is
formable into the configurations described herein. Also, the
conduit may be formed from a cylinder with the passageway being
formed through the conduit. The conduit may also be formed from a
sheet of material in which a specific pattern is cut. The cut sheet
may then be rolled and formed into a tube. The materials used for
the conduit can be those described above as well as a polymeric
material, a biostable or implantable material, a material with
rigid properties, a material with elastomeric properties, or a
combination thereof. If the conduit is a polymeric elastic tube
(e.g. a thermoplastic elastomer), the conduit may be extruded and
cut to size, injection molded, or otherwise formed.
Additionally, the conduits described herein may be comprised of a
shape memory alloy, a super-elastic alloy (e.g., a NiTi alloy), a
shape memory polymer, or a shape memory composite material. The
conduit may be constructed to have a natural self-assuming deployed
configuration, but is restrained in a pre-deployed configuration.
As such, removal of the restraints (e.g., a sheath) causes the
conduit to assume the deployed configuration. A conduit of this
type could be, but is not limited to being, comprised from an
elastic polymeric material, or shape memory material such as a
shape memory alloy. It is also contemplated that the conduit could
comprise a shape memory alloy such that, upon reaching a particular
temperature (e.g., 98.5.degree. F.), it assumes a deployed
configuration.
Also, the conduit described herein may be formed of a plastically
deformable material such that the conduit is expanded and
plastically deforms into a deployed configuration. The conduit may
be expanded into its expanded state by a variety of devices such
as, for example, a balloon catheter.
The conduit's surface may be modified to affect tissue growth or
adhesion. For example, an implant may comprise a smooth surface
finish in the range of 0.1 micrometer to 0.01 micrometer. Such a
finish may serve to prevent the conduit from being ejected or
occluded by tissue overgrowth. On the other hand, the surface may
be roughened or porous. The conduit may also comprise various
coatings and tissue barriers as discussed below.
Tissue Barrier
FIG. 3A illustrates another variation of a conduit 200 having a
tissue barrier 240. The tissue barrier 240 prevents tissue ingrowth
from occluding the collateral channel or passage of the conduit
200. The tissue barrier 240 may coaxially cover the center section
from one end to the other or it may only cover one or more regions
of the conduit 200. The tissue barrier may completely or partially
cover the conduit so long as the ends are at least partially open.
Moreover, the tissue barrier may only be placed on the center
section of the conduit. The tissue barrier 240 may be located about
an exterior of the conduit's surface, about an interior of the
conduit's surface, or the tissue barrier 240 may be located within
openings in the wall of the conduit's surface. Furthermore, in some
variations of the invention, the center section 208 itself may
provide an effective barrier to tissue ingrowth. The tissue
barrier, of course, should not cover or block the entrance and exit
of the passageway such that air is prevented from passing through
the conduit's passageway. However, in some constructs, the tissue
barrier may partially block the entrance or exit of the passageway
so long as air may continue to pass through the conduit's
passageway.
The tissue barrier may be formed from a material, mesh, sleeve, or
coating that is a polymer or an elastomer such as, for example,
silicone, fluorosilicone, polyurethane, PET, PTFE, or expanded
PTFE. Other biocompatible materials will work, such as a thin foil
of metal, etc. The coatings may be applied, for example, by either
dip coating, molding, spin-coating, transfer molding or liquid
injection molding. Alternatively, the tissue barrier may be a tube
of a material and the tube is placed either over and/or within the
conduit. The tissue barrier may then be bonded, crimped, heated,
melted, shrink fitted or fused to the conduit. The tissue barrier
may also be tied to the conduit with a filament of, for example, a
suture material.
Still other techniques for attaching the tissue barrier include:
solvent swelling applications and extrusion processes; wrapping a
sheet of material about the conduit, or placing a tube of the
material about the conduit and securing the tube to the conduit.
The tissue barrier may be secured on the interior of the conduit by
positioning a sheet or tube of material on the inside of the center
section and securing the material therein.
The tissue barrier may also be formed of a fine mesh with a
porosity or treatment such that tissue may not penetrate the pores.
For example, a ChronoFlex.TM. DACRON.RTM. or TEFLON.RTM. mesh
having a pore size of 100-300 microns may be saturated with
collagen or another biocompatible substance. This construct may
form a suitable tissue barrier. The mesh may be coaxially attached
to a frame such as the open frame structures disclosed above. Still
other suitable frames include a continuous spiral metallic or
polymeric element. Given the mesh's radial strength or lack
thereof, the use of a reinforcement element serves to prevent the
implant from collapsing. Also, as described below, other substances
may be applied to the exterior surface of the conduit to control
elution of various medicines.
FIGS. 3B and 3C respectively illustrate a side view and a front
view of another conduit 300 having a partial tissue barrier
coating. The conduit 300 includes a center section 310, a plurality
of extension members 320, and a partial tissue barrier 330. The
conduit 300 is thus different than that shown in FIG. 3A in that
the center section is longer and that the tissue barrier 330 only
partially covers the extension members 320. In particular, the
center section 310 shown in FIGS. 3B-3C is cylindrical or
tubular-shaped. This shape may be advantageous when a relatively
long passageway is desired. Also, it is to be understood that the
overall (or three dimensional) shape of the center section, when
deployed, is not limited to the shape shown here. Rather, it may
have various shapes such as, for example, rectangular, tubular,
conical, hour-glass, hemi-toroidal, etc.
Additionally, the tissue barrier 330 covers only a first region 350
of the extension members and leaves a second region 340 of the
extension members uncovered. The second or free region 340 of the
extension members 320 is shown as being open-framed. However, the
invention is not so limited. The second region of the extension
members may be solid and it may include indentations, grooves, and
recesses for tissue ingrowth. Also, the extension members may
include small holes for tissue ingrowth. For example, the second
region of the extension members may have a dense array of small
holes. In any event, the conduits described herein may include at
least one region or surface which is susceptible to tissue ingrowth
or is otherwise adherent to the tissue. Accordingly, tissue
ingrowth at the second region 340 of the extension members is
facilitated while tissue growth into the passageway 325 is
thwarted.
As shown in FIG. 3D, tissue growth 360 into the uncovered region
340 further secures the extension members to the tissue wall 370.
Free region 340 of the extension members may also include tissue
growth substances such as epithelial growth factors or agents to
encourage tissue ingrowth. Accordingly, conduit 300 may be
configured to engage the tissue wall 370 as well as to allow tissue
to grow into predetermined regions of the conduit.
Visualization Feature
The conduit shown in FIG. 3A also includes a visualization ring or
marker 242. The marker 242 is visually apparent during a procedure.
The marker is observed as the conduit is placed in a collateral
channel and, when the marker is even with the opening of the
channel, the conduit may be deployed. In this manner, the
visualization feature facilitates alignment and deployment of the
conduits into collateral channels.
The visualization ring or mark may be a biocompatible polymer and
have a color such as white. Also, the visualization feature may
protrude from the center section or it may be an indentation(s).
The visualization mark may also be a ring, groove or any other
physical feature on the conduit. Moreover, the visualization
feature may be continuous or comprise discrete segments (e.g., dots
or line segments).
The visualization feature may be made using a number of techniques.
In one example, the mark is a ring formed of silicone and is white.
The polymeric ring may be spun onto the tissue barrier. For
example, a clear silicone barrier may be coated onto the conduit
such that it coaxially covers the extension members and the center
section as shown in FIG. 3A. Next, a thin ring of white material
such as a metal oxide suspended in clear silicone may be spun onto
the silicone coating. Finally, another coating of clear silicone
may be applied to coat the white layer. The conduit thus may
include upwards of 1-3 layers including a tissue barrier, a
visualization mark layer, and a clear outer covering.
The shape of the visualization mark is not limited to a thin ring.
The visualization mark may be large, for example, and cover an
entire half of the conduit as shown in FIG. 3B. The visualization
mark may, for example, be a white coating disposed on the proximal
or distal half of the conduit. The visualization mark thus may
extend from an end of the extension members to the center section
of the conduit. As explained in more detail below, when such a
device is deposited into a channel created in lung tissue, the
physician may observe when one-half of the conduit extends into the
channel. This allows the physician to properly actuate or deploy
the conduit to secure the conduit in the tissue wall.
Accordingly, the visualization member is made visually apparent for
use with, for example, an endoscope. The visualization feature,
however, may also be made of other vision-enhancing materials such
as radio-opaque metals used in x-ray detection. It is also
contemplated that other elements of the conduit can include
visualization features such as but not limited to the extension
members, tissue barrier, control segments, etc.
In some variations of the invention, it was found that
incorporation of a bioactive, as discussed herein, or other
substance into the coating caused a coloration effect in the
composition layer (e.g., the polymer turns white). This coloration
obscures the support member structure in the layer making it
difficult to identify the edges and center of the support member or
implant. As discussed herein, placement of the implant may depend
upon positioning the center of the implant within the opening in
tissue. If the support member structure is identifiable, then one
is able to visually identify the center of the implant. When the
composition colors obscures the support member or renders the
implant otherwise opaque, it may become difficult to properly place
the device. This may be especially true when the composition layer
extends continuously over the support member.
Additionally, the coloration may render the visualization mark
difficult to identify especially under direct visualization (e.g.,
using a scope) In some cases it was undesirable to simply add
additional substances on or in the composition layer for marking
because such substances could possibly interfere with the implant's
ability to deliver the substance as desired. To address these
issues, a variation of the invention includes a delivery device for
delivering an expandable implant (such as those described herein
and in the cases referenced herein), where the delivery device
includes an expandable member having an expandable implant located
about the expandable member. Where the implant and the expandable
member are of different visually identifiable colors or shades such
that they distinction is easy to identify under endoscopic or
bronchoscopic viewing.
In one example, a balloon catheter has a colored sleeve located
about the balloon. The sleeve comprises a visually identifiable
color where selection of the colors should ease identification of
the implant an endoscopic visualization system (e.g., blue or a
similar color that is not naturally occurring within the body.) The
implant is placed about the sleeve where the proximal and distal
areas of the implant would be identifiable by the difference in
color. Such a system allows a medical practitioner to place the
implant 200 properly by using the boundary of the implant 200 to
guide placement in the tissue wall. The sleeve may be fashioned
from any expandable material, such as a polymer. Optionally, the
sleeve may also provide an elastic force to return the balloon to a
reduced profile after expansion of the balloon. Such a system
allows for identification without affecting the properties of the
implant.
It should be noted that variations of the invention include
coloring the balloon itself, or other expandable member, a color
that meets the above criteria.
In another variation, the visualization mark may comprise providing
a contrast between the implant and a delivery catheter. In one
example the implant is appears mostly white and while mounted on a
contrasting color inflation balloon. In this example the implant
would be placed over a blue deflated balloon catheter. The proximal
and distal areas of the implant would be flanked by the deflated
blue balloon, thus giving the appearance of a distinct distal and
proximal end of the implant. This would allow a physician to place
the implant properly by using the blue flanks as a guide for
placing the central white portion in the tissue wall. Similarly, a
colored flexible sheath covering the balloon would also
suffice.
It is noted that while the visualization features described above
are suitable for use with the implants described herein, the
inventive features are not limited as such. The features may be
incorporated into any system where placement of an implant under
direct visualization requires clear identification of the implant
regardless of whether the implant is opaque or colored.
Bioactive Agents
As discussed above, the bio-active substance or combination of
bioactive substances is selected to assists in modifying the
healing response as a result of the trauma to the lung tissue
resulting from creation of the collateral channel. As noted above,
the term lung tissue is intended to include the tissue lining the
airway, the tissue beneath the lining, and the tissue within the
lung but exterior to the airway (e.g., lung parenchyma.) The
purpose of modifying the healing response is to further extend the
patency of the channel or implant to increase the duration which
trapped gasses may exit through the implant into the airways. The
term antiproliferative agent is intended to include those bioactive
substances that directly modify the healing response described
herein.
The bioactive substances are intended to interact with the tissue
of the surgically created channels and in particular, lung tissue.
These substances may interact with the tissue in a number of ways.
They may, for example, 1.) accelerate cell proliferation or wound
healing to epithelialize or scar the walls of the
surgically-created channel to maintain its patent shape or 2.) the
substances may inhibit or halt tissue growth when a channel is
surgically created through an airway wall such that occlusion of
the channel due to tissue overgrowth is prevented. Additionally,
other bioactive agents may inhibit wound healing such that the
injury site (e.g., the channel or opening) does not heal leaving
the injury site open and/or inhibit infection (e.g., reduce
bacteria) such that excessive wound healing does not occur which
may lead to excessive tissue growth at the channel thereby blocking
the passageway. By creating an extra-anatomic passage and
inhibiting wound healing as discussed above it is possible to
create and maintain the extra-anatomic opening in an airway wall at
a target site such that patency of the extra-anatomic opening is
artificially extended beyond an otherwise natural healing
response
A variety of bioactive substances may be used alone or in
combination with the devices described herein. Examples of
bioactive substances include, but are not limited to,
antimetabolites, antithrobotics, anticoagulants, antiplatelet
agents, thorombolytics, antiproliferatives, antinflammatories,
agents that inhibit hyperplasia and in particular restenosis,
smooth muscle cell inhibitors, growth factors, growth factor
inhibitors, cell adhesion inhibitors, cell adhesion promoters and
drugs that may enhance the formation of healthy neointimal tissue,
including endothelial cell regeneration. The positive action may
come from inhibiting particular cells (e.g., smooth muscle cells)
or tissue formation (e.g., fibromuscular tissue) while encouraging
different cell migration (e.g., endothelium, epithelium) and tissue
formation (neointimal tissue).
Still other bioactive agents include but are not limited to
analgesics, anticonvulsives, anti-infectives (e.g., antibiotics,
antimicrobials), antineoplastics, H2 antagonists (Histamine 2
antagonists), steroids, non-steroidal anti-inflammatories,
hormones, immunomodulators, mast cell stabilizers, nucleoside
analogues, respiratory agents, antihypertensives, antihistamines,
ACE inhibitors, cell growth factors, nerve growth factors,
anti-angiogenic agents or angiogenesis inhibitors (e.g.,
endostatins or angiostatins), tissue irritants (e.g., a compound
comprising talc), poisons (e.g., arsenic), cytotoxic agents (e.g.,
a compound that can cause cell death), various metals (silver,
aluminum, zinc, platinum, arsenic, etc.), epithelial growth factors
or a combination of any of the agents disclosed herein.
Examples of agents include pyrolitic carbon,
titanium-nitride-oxide, taxanes, fibrinogen, collagen, thrombin,
phosphorylcholine, heparin, rapamycin, radioactive 188Re and 32P,
silver nitrate, dactinomycin, sirolimus, everolimus, Abt-578,
tacrolimus, camptothecin, etoposide, vincristine, mitomycin,
fluorouracil, or cell adhesion peptides. Taxanes include, for
example, paclitaxel, 10-deacetyltaxol, 7-epi-10-deacetyltaxol,
7-xylosyl-10-deacetyltaxol, 7-epi-taxol, cephalomannine, baccatin
III, baccatin V, 10-deacetylbaccatin III, 7-epi-10-deacetylbaccatin
III, docetaxel.
Of course, bioactive materials having other functions can also be
successfully delivered in accordance with the present invention.
For example, an antiproliferative agent such as methotrexate will
inhibit over-proliferation of smooth muscle cells and thus inhibit
restenosis. The antiproliferative is desirably supplied for this
purpose until the tissue has properly healed. Additionally,
localized delivery of an antiproliferative agent is also useful for
the treatment of a variety of malignant conditions characterized by
highly vascular growth. In such cases, an implant such as a implant
could be placed in the surgically created channel to provide a
means of delivering a relatively high dose of the antiproliferative
agent directly to the target area. A vasodilator such as a calcium
channel blocker or a nitrate may also be delivered to the target
site. The agent may further be a curative, a pre-operative debulker
reducing the size of the growth, or a palliative which eases the
symptoms of the disease. For example, tamoxifen citrate, Taxol.RTM.
or derivatives thereof. Proscar.RTM., Hytrin.RTM., or Eulexin.RTM.
may be applied to the target site as described herein.
Variations of the invention may also include fibrinolytics such as
tPA, streptokinase, or urokinase, etc. Such fibrinolytics prevent
or reduce the accumulation of fibrin within the opening.
Accumulation of fibrin in the opening may result from inflammation
of the tissue. The fibrin may form a structure which makes it
easier for tissue to grow into the opening using the fibrin
structure as a framework. Use of fibrinolytics, either topically,
locally, or on the implant, serves to remove or hinder the network
of fibrin from forming within the opening (or implant) and
therefore aids in modifying the healing response.
In the event that poisonous and toxic compounds are delivered, they
should be controlled so that inadvertent death of tissue does not
occur. The poisonous agent should be delivered locally or only be
effective locally. One method for delivering the bioactive agent
locally is to associate the bioactive agent with an implant. For
example, the implants described herein may include a bioactive
substance or medicine deposited onto the interior, the exterior, or
both the interior and exterior surfaces of the implant. The
bioactive substance may remain on the implant so that it does not
leach. Cells that grow into the surgically created channel contact
the poison and die. Alternatively, the bioactive agent may be
configured to gradually elute as discussed below.
When used in the lungs, the implant modifies the healing response
of the lung tissue (e.g., at the site of newly created
hole/channel) for a sufficient time until the healing response of
the lung tissue subsides or reduces such that the hole/channel
becomes a persistent air path. For example, the implant and
bioactive substance will modify the healing response for a
sufficient time until the healing response is reduced and, from a
visual observation, the body treats the opening essentially as a
natural airway passage rather than as an injury to the airway
wall.
In one variation of the invention which modifies the healing
response as describe above, the implant provides a steady release
rate of bio-active substance as well as has a sufficient amount of
available bio-active substance to modify the healing response of
the lung tissue. As noted herein, the term lung tissue is intended
to include the tissue lining the airway, the tissue beneath the
lining, and the tissue within the lung but exterior to the airway
(e.g., lung parenchyma.) Such a delivery profile allows for a
concentration gradient of drug to build in these tissues adjacent
to the delivery site of the implant.
It is believed that forming the concentration gradient affects the
healing response of the lung tissue so that the implant does not
become occluded as a result of the healing response. Because the
implant is often placed in the airway wall it is exposed to the
healing process of the multiple tissues. Providing a sufficient
amount of bio-active substance allows for the formation of a
concentration of the bio-active substance across these various
tissues. In one variation of the invention it is believed that the
fluids from these tissues enter into the composition layer of the
device. The fluids then combine with the bio-active substances and
migrate out of the composition layer to settle into the lung
tissue. A concentration gradient forms when the drug `saturates`
local tissue and migrates beyond the saturated tissues.
Furthermore, by providing a sufficient delivery rate, the healing
response may be affected or suppressed during the critical time
immediately after the wounding caused by creation of the collateral
channel when the healing response is greatest.
To select a proper combination of drug and polymer, it is believed
that the solubility parameter of the polymer must be matched with
the bio-active substance to provide an acceptable slow elution rate
from the polymer. Next, the polymer itself must be selected to have
the proper attributes, such as a proper diffusion coefficient (to
slow fluid entering and departing from the implant), and proper
mechanical expansion properties (to allow for the significant
expansion of the polymer to accommodate formation of the grommet
shape.)
The solubility parameter is defined as the square root of the
cohesive energy of the molecules in a compound. The level of
control that a polymer has over the elution of a drug is the
difference between the solubility parameters of the polymer and the
solubility parameter of the drug. To select a polymer with the
approximate diffusion a polymer with a high internal density could
be selected to be less permeable to a complex molecule such as
paclitaxel. Using a polymer with high internal density also
accommodated the significant expansion required of the polymer to
form the structure necessary to grommet about the airway wall. An
example of the polymer selection is found below.
It is also important to note that paclitaxel is a taxane that is
regarded as a microtubule stabilizer. The benefits of a microtubule
stabilizing substance for use in vascular drug eluting stents is
discussed, for example, in U.S. Pat. No. 5,616,608 to Kinsella et
al. This type of drug operates to enhance microtubule
polymerization which inhibits cell replication by stabilizing
microtubules in spindles which block cell division. In contrast to
the vascular applications, the implant for use in the present
invention may use microtubule stabilizing substances such as
taxanes (e.g., paclitaxel) as well as those microtubule
destabilizing substances that are believed to promote microtubule
disassembly in preventing cell replication. Such destabilizing
substances include, but are not limited to vincristine,
vinblastine, podophylotoxin, estramustine, noscapine, griseofulvin,
dicoumarol, a vinca alkaloid, and a combination thereof.
Additionally, the exterior surface of the implant may be treated
via etching processes or with electrical charge to encourage
binding of the bioactive substances to the implant. The exterior
surface may also be roughened to enhance binding of the medicine to
the surface as discussed in U.S. Patent Application Publication No.
2002/0098278. See also U.S. Patent Application Publication Nos.
2002/0071902, 2002/0127327 and U.S. Pat. No. 5,824,048 which
discuss various techniques for coating medical implants.
Although the implant may comprise a frame or body with a bioactive
matrix disposed or otherwise associated therewith, the invention is
not so limited. In one variation, the support member is formed from
a polymer and the composition is joined to the polymeric support
member. Alternatively, the bioactive substances may be placed
directly onto the polymeric support member.
Various additional substances may be used incorporated into the
device to reduce an adverse reaction resulting from possible
contact with the implant and the airway wall. Adverse reactions
include, but are not limited to, granulation, swelling, and mucus
overproduction. These substance may also be inhaled, injected,
orally applied, topically applied, or carried by the implant. These
substances may include anti-inflammatory, infection-fighting
substances, steroids, mucalytics, enzymes, and wound
healing-accelerating substances. Examples of these substances
include but are not limited to, acetylcysteine, albuterol sulfate,
ipratropium bromide, dornase alfa, and corticosteroids.
As noted above, conventional vascular drug eluting devices are not
designed for exposure multiple tissue environments. Moreover, those
devices are placed in an environment where a constant flow of blood
creates an environment requiring a different delivery mechanism and
rate. As noted herein, experiments with conventional coronary drug
eluting implants demonstrated that such devices were
unsuitable.
Channel Creation Devices and Methods
As discussed above, the use of low temperature devices, (e.g.,
mechanical devices, newer generation RF-type devices, etc.) to
create the channel may result in less trauma to surrounding tissue
and minimize the healing response of the tissue. FIGS. 4A-4C
illustrates creation of the collateral channel and selecting a
treatment site in the airway 100. As will be discussed in more
detail below, a single device may be used to select the site and
create the channel. Moreover, another variation of the invention
includes using such a device to deploy the conduit at the target
site. However, the invention also contemplates using separate
devices to perform each step or a combination of steps.
As shown in FIG. 4A, a device 602 is advanced, for example, via a
bronchoscope 404, into the airway 100. The device can be delivered
through a natural respiratory opening such as an oral opening and
into the airway 100. A potential treatment site is then inspected
to determine whether or not a blood vessel is in proximity to the
site. Naturally, if a blood vessel is detected, the surgeon has the
option of selecting a different site. The device 602 may be a
Doppler ultrasound device, a thermal device, an imaging device,
etc.
FIG. 4B illustrates another variation of selecting a site for a
channel. In this variation, a piercing member (e.g., a blade
affixed to a shaft, a needle, cannula, sharpened tube or rod,
etc.,) 604 is advanced into the airway wall. Once the piercing
member 604 is inserted into the airway wall, the surgeon may
inspect the area for blood to determine whether the device
punctured a blood vessel. After the opening is created the surgeon
may also remove collect a biopsy of material behind the airway
wall. If the opening is large enough as created by a balloon, as
described herein, the surgeon may use forceps to visually obtain
the sample. This may be preferable to a blind method of obtaining
biopsies, considering that the risk of bleeding may be reduced
because the area has been scanned for blood vessels.
The piercing member 604 may have a lumen and may be open at a
distal end or closed. In those cases where the piercing member 604
is hollow and has an opening at or near the distal end, the surgeon
may aspirate the site using the piercing member 604 to determine
whether a blood vessel is present and/or penetrated. For example,
flashback catheters contain chambers which will fill with blood
upon the penetration of a vessel by the distal tip of the catheter.
The piercing member may be incorporated to have a flashback chamber
to detect the presence of blood flow from a penetrated vessel.
Using these approaches, a target site may not be selected until
after a hole is made in the airway 100 wall. It should be noted
that a piercing member may be of a diameter which results in
closure of the puncture site upon removal of the piercing member.
Alternatively, the piercing member may be of a sufficient size or
construction that the hole remains open upon removal of the
piercing member. In any case, the piercing member or another device
may be used to mark the site of the opening (e.g., via ink, dye,
physical marker, via application of electrical energy, etc.)
Furthermore, the invention includes use of both a detecting device
as described above in combination with a piercing member. For
example, the site may be inspected by the detecting device prior to
insertion of a piercing member.
The piercing member lumen may also used to deliver therapeutic
fluids to the lungs. For example, in case of bleeding after channel
creation the physician may apply epinephrine or saline the lungs.
Alternatively the physician may use the piercing member to apply
epinephrine to the airway wall prior to creation of the channel, to
prevent bleeding. This may be done by injecting directly into the
airway wall at or about the site of passage creation; singly or in
a surrounding pattern of multiple applications. The physician may
also use the piercing member lumen to apply any of the bioactive
agents discussed herein, before or after passage creation.
Because it may be desirable to reach remote airways within the
lung, it may be necessary to fully articulate the scope 404 to
access and inspect a desirable site. Therefore, to inspect the site
and create an opening, it may be desirable to maintain the scope
404 in a fixed position and simply advance/retract various
components of the scope or devices in the scope. Accordingly, a
piercing member may be selected to have a length that will
sufficiently pass through the airway wall, while being small enough
that it will also pass through a fully articulated bronchoscope.
Furthermore, the piercing member may have sections of varying
stiffness where a distal portion, (that is sufficient stiff to
penetrate the tissue) may be of a length such that it is able to
advance through a fully articulated bronchoscope. For example, the
piercing member may comprised of a sharpened cannula which has a
length from between 2 mm to 30 mm. The diameter may range between
16 Ga to 25 Ga or larger. The cannula may be affixed to a catheter
having a relatively flexible proximal portion. In any case, the
length of the piecing member 604 may vary as needed.
The piercing member is not limited to a cannula, it may be of solid
construction, such as a sharpened rod or wire. Additionally the
piercing member may be adapted with an elongate member, such as a
wire, rod, or tube, which extends throughout the device. The
purpose of the elongate member is to provide column strength to the
piercing member and necessary bending resistance to the catheter,
because it has been found that the device must have high column
strength to effectively pierce the airway wall, otherwise the
device will deflect and not create a passageway. The elongate
member may be utilized to expose and retract the piercing member
within the catheter, as the elongate member may extend throughout
the device to a user interface. The elongate member and piercing
member may also be constructed from one piece of material, thereby
making them one part. Alternatively the elongate member may be a
separate part welded, bonded, mechanically attached, or a
combination thereof, to the piercing member.
However, it is understood, that the current invention is not
limited to any particular length of the piercing member.
Furthermore, the piercing member may be comprised of a resilient
polymer, a polymer with a reinforced structure (e.g., a braid,
coil, etc.), a super-elastic alloy, a metallic material with
sufficient resilience, etc, such that it may navigate through a
fully articulated bronchoscope yet return to its original profile
upon exiting the working channel of the scope.
In some variations of the invention, the piercing member of the
device may be retractable within a lumen of an elongate shaft so as
to prevent damage to the bronchoscope or to tissue as the device
advances to the target site. Additionally the piercing member may
be retracted after the initial piercing of the airway wall, and
blunt trauma may be used to further push the remaining portion of
the catheter into the airway wall. This technique may help avoid
additional bleeding and pneumothoraxes from an exposed piercing
member. The catheter may be advanced to tortuous locations,
therefore the device may incorporate low friction materials to make
it easier to reach the treatment site. The materials may be
selected from a group of low friction polymers, for example PTFE.
Low friction materials may also be applied as a coating onto the
pierced member or elongate member, for example PTFE or titanium
nitride. Reducing the contact surface area between the members may
also help to reduce friction. Adding or removing material from the
surfaces of members is one way to reduce contact surface area. For
example attaching a closed coiled spring around the piercing member
or elongate member, effectively reduces the surface area contacted
between the elongate member and lumen because only the peaks of the
coils contact the lumen.
In additional variations of the invention, as shown in FIG. 4C, a
balloon catheter may be configured with a piercing member 604. In
this variation the balloon 614 advances into the opening created by
the piercing member (in which case the piercing member either
retracts into the catheter or advances with the catheter.) The
balloon 614 would then deploy to dilate the opening for ease of
later inserting a conduit. Alternatively, a conduit may be located
on the balloon itself and deployed on inflation of the balloon.
Examples of variations of such a balloon catheter may be found
below. Furthermore, the needle may be affixed to a tapered
introducer type device which is able to dilate the opening.
The piercing member 604 may also be used to deliver bioactive
substances (as described herein) to the site of the opening. In
such a case, the piercing member 604 may deliver the bioactive
substance during creation of the opening (e.g., see FIG. 4B) or
after dilation of the opening (see e.g., FIG. 4C). In another
variation of the invention, the piercing member 604 may be have a
multi-lumen cross-section with different lumens being reserved, for
example, for inflating the balloon, aspirating the site for blood,
drug delivery, and suction of mucous/fluids at the site. In any of
the variations described herein, an obturator (not shown) may be
used to fill a lumen during advancement of the piercing member into
tissue so that the lumen does not become blocked with tissue or
other debris. The obturator may be a guide-wire, polymeric column
of material, etc.
FIG. 4D illustrates a variation of a balloon catheter 606 having a
piercing member 604. In this variation, the balloon catheter 606
comprises two lumens 608, 610. One lumen 608 is fluidly coupled to
the interior of the balloon 614 while the second lumen 610 extends
through the piercing member 604. It is understood that the device
606 may be configured to have any number of lumens as required. As
discussed above, the piercing member 604 may either be fixedly
attached to the distal end of the balloon catheter 606.
Alternatively, the piercing member 604 may be retractable into the
balloon catheter 606 so that it does not cause damage to lung
parenchyma when the catheter 606 is inserted into the airway 100
wall. As illustrated, the balloon catheter 606 may have a tapered
section 612 between the piercing member 604 and the balloon 614 to
assist in insertion of the balloon 614 into the opening 112.
FIG. 4E illustrates an additional variation of a piercing member
604 according the present invention. As illustrated, the piercing
member 604 may have a number of ports 616 (e.g., openings, holes,
etc.). The ports 616 may allow for either aspiration of blood or
delivery of bio-active substances as described herein. Furthermore,
although the piercing members 604 shown herein are configured with
a beveled tip, it is contemplated that the tip may be any type of
tip sufficient to penetrate the airway wall. For instance, the tip
may be non-beveled with sharpened edges, the tip may be a trocar
tipped needle, or any other available needle tip configuration. The
piercing member 604 of FIG. 4E is also shown with an obturator
placed therein. In this configuration, the obturator 618 blocks the
lumen of the piercing member 604 at the distal end. Moreover, as
shown, a portion of the obturator 618 may be sized such that it is
smaller than a lumen of the piercing member 604 to allow for
delivery of substances or aspiration through the ports 616.
FIG. 4F illustrates yet another variation of a balloon catheter 606
having a piercing member 604. In this variation, as indicated by
the arrow, the piercing member 604 is capable of being retracted
into the catheter 606. The ability to retract the piercing member
604 into the catheter 606 reduces the possibility of the piercing
member 604 causing damage to any lung tissue that is behind the
airway wall. Clearly, this variation combines the channel-making
step with the conduit deployment step. Also, as shown in the
figure, the catheter 606 may have a conduit 200 placed over the
balloon 614. Such a variation may create the opening or channel and
then deploy the conduit 200 with a single device.
FIG. 4G illustrates another variation of a balloon catheter 606
where the piercing member 604 is slidably located within the
catheter 606. In this variation, the catheter 606 contains an outer
and inner sheaths 620, 622 which define two lumens. The lumen
defined by the inner sheath 622 extends to the distal end of the
catheter 606 and may be used to deliver bioactive substances, for
suction, or for irrigation.
It is also contemplated that variations of the invention include a
piercing member which is affixed to the catheter. Alternatively,
the piercing member could have a flexible body that extends through
the catheter to a proximal hub which is able to be coupled to a
vacuum source, a source of medication, etc. Furthermore, either the
piercing member and/or balloon catheter may be "pre-loaded" with a
bioactive substance. Such a feature allows improves the precision
of amount of substance delivered to the desired site.
As mentioned above, the piercing member 604 may be of a sufficient
size or construction that the hole remains open upon removal of the
piercing member. Once variation of this as shown in FIG. 4H, where
the device has a conical tip 658 with a lumen extending through
out. A piercing member 604 is extendable past the distal tip to
pierce the airway wall, after the initial opening is made, the rest
of the device can be driven into the airway wall, gradually
expanding the hole to a desirable diameter which allows the conduit
to be subsequently placed.
The makeup of airway tissue may require a considerable amount of
force to create a channel with the piercing device. Therefore, it
will generally be easier to create a channel if the device has
sufficient column strength to avoid bending of the device when
applying a force at the proximal end of the device.
Additional variations of the invention may incorporate a
nondistensible balloon to overcome the toughness of the airway
tissue. Nondistensible balloons are generally made up of relatively
inelastic materials consisting of PET, nylons, polyurethanes,
polyolefins, PVC, and other crosslinked polymers. The makeup of
airway tissue may be very tough and resist radial expansions.
Therefore it will be generally easier to expand the channel in the
airway wall using high pressure nondistensible balloons (>6
atm), which generally inflate in a uniform shape.
Nondistensible balloons will occupy a greater mass than distensible
balloons because they in an inelastic predetermined form. Too much
balloon mass will have too large of a working diameter, which in
turn will hinder entry into a channel. Working diameter is the
smallest effective diameter opening the uninflated nondistensible
balloon can be inserted into. Therefore it is desirable to have the
uninflated nondistensible balloon to have a working diameter close
to the diameter of the piercing device 604. This can be attained by
using a thin walled balloon, using a balloon with a small distal
profile, by using a balloon with a distal end which is close in
actual diameter to the diameter of the piercing member, or by using
a balloon which folds into a low profile state, or a combination of
these.
As shown in FIG. 4I, a device of insufficient sharpness will "tent"
the airway wall 450. Tenting occurs when a device is placed against
an airway wall with significant force but with no puncturing of the
airway wall. The airway wall will deflect and become displaced
until the device is withdrawn. If the tissue becomes tented there
remains a significant amount of potential energy placed by the
device onto the airway wall. The potential energy may unexpectedly
becomes realized, when the device eventually punctures the airway,
which may cause the device to suddenly plunge into the parenchyma
to an unintended depth. Plunging may in turn cause unintended
damage to the patient. A depth limiting feature 654 may overcome
this problem.
Variations of the invention include a depth limiting feature that
may prevent inadvertent advancement of the device when creating the
channel. One example of this may be a circular tube 654 placed over
the device and set at a fixed distance (e.g. 10 mm) from the distal
tip of the piercing member, proximal to the balloon, as shown in
FIG. 4J. If the device does tent and plunge into the airway wall
the front face of the tube may halt the plunging effect by acting
as a barrier. Another example would be a secondary balloon,
proximal to the channel expansion balloon, placed in a similar
position to the circular tube as described above. Another example
would be a folding basket formed from the outer lumen of the
device, or constructed from wire.
As shown in FIG. 4K, variations of the invention may include a
distal collar 650 on the distal portion of the piercing member 604
to precisely limit the maximum extension and retraction of the
piercing member 604. The distal collar 650 would be attached to the
piercing member and travel between two set collar stops 652 which
are attached to the lumen 656 the piercing member travels in. This
feature has multiple benefits; first, it has the safety setting a
maximum distance for the piercing member to extend, around 2-3 mm
has been found to be sufficient in most cases. Thus, the maximum
penetration of the piercing member 604 is limited which may prevent
unintentional damage to the lung tissue.
The collar 650 protects the bronchoscope by preventing deflection
of the distal tip. Deflection can take place when there is a
significant amount of gap between the inner sheath 622 and the
distal tip of the piercing member in the retracted mode. When the
device is being maneuvered through a bronchoscope in a torturous
configuration, the lumen 656 can deflect while the stiffer piercing
member will not, and thus the piercing member may pierce through
the deflected lumen 656 and subsequently into the bronchoscope. By
setting a small gap (e.g. <1 mm) this deflection may be
eliminated, and the scope protected.
The collar 650 also allows the piercing member to be reliably
extended. It was found that when a similar feature was placed at
the proximal section of the device the piercing member could not
reliably be extended to a set distance beyond the distal tip. This
is because when in a torturous configuration the outer sheath 620
of the device may have a tendency to stretch or compress. As a
result the tubing may stretch to such a degree that when the
piercing member is fully extended it still may not fully extend
past the distal tip of the lumen 656. By locating the collar 650 in
the distal portion of the lumen 656 (e.g. less than 2 inches from
the distal tip) the stretching or compression is minimized or
eliminated.
Conduit Deployment Devices and Methods
FIGS. 5A-5C illustrate a way to deploy a conduit in a channel.
Referring to FIG. 5A, a delivery device 400 is loaded with a
conduit 200. An access scope-type device 404 (e.g., an endoscope, a
bronchoscope, or other device) may optionally be used to place the
delivery device 400 into a collateral channel 112. A guide wire 402
may be used to place the delivery device 400 into the collateral
channel 112. The guide wire 402 may be a conventional guide-wire or
it may simply be comprised of a super-elastic material. The use of
a guide wire is optional as the invention contemplates placement of
the conduit 200 using only the delivery device 400.
FIG. 5A also illustrates articulation (or bending) of the deliver
device 400 to access the collateral channel 112. However, the
invention also contemplates articulation of the access device 404.
The access device 404 may be articulated such that the delivery
device 400 may advance straight into the collateral channel 112.
Accordingly, the delivery device 400 may exit straight from the
access device 404 or it may be articulated into the opening.
FIG. 5B illustrates deployment of the conduit 200. In particular,
balloon member 406 is shown in an expanded state resulting in (1)
the conduit's center section being radially expanded and (2) the
conduit's extension members being outwardly deflected such that
opposing extension members sandwich portions of the tissue wall
422. Diametric-control members 424 are also shown in this figure.
The diametric or center-control segments limit the center section's
radial expansion. In this manner, conduit 200 is securely placed in
the channel to maintain a passageway through the airway wall
422.
FIG. 5C illustrates the deployed conduit 200 once the delivery
device 400 is removed from the site. It should be noted that
dilation of the collateral channel or opening 112 may be performed
by mere insertion of the conduit 200 and/or delivery device
400.
It should be noted that deployment of conduits is not limited to
that shown in FIGS. 5A-5C, instead, other means may be used to
deploy the conduit. For example, spring-loaded or shape memory
features may be actuated by mechanical or thermal release and
unlocking methods. Additionally, mechanical wedges, lever-type
devices, scissors-jack devices, open chest surgical placement and
other techniques may be used to deploy the conduit. Again, the
conduit 200 may be comprised of an elastic or super-elastic
material which is restrained in a reduced profile for deployment
and expands to its deployed state upon mechanical actuator or
release.
In one additional variation of the invention, as shown in FIG. 5D,
a conduit 201 may be deployed within a second structure such as a
second conduit or stent. Such an approach may be used to increase
retention of the conduits within the channel as well as prevent
closing of the channel. For example, an initial conduit 200 or
stent may be deployed within the channel 112. This first conduit or
stent may have certain properties that make it more acceptable to
implantation within the body without generating an aggressive
tissue healing response. For instance, the stent may be a drug
eluting stent, or the conduit may be constructed from a
bio-compatible metal without any additional tissue barrier. Once
the initial stent or conduit is placed within the channel 112 a
second conduit may be deployed within the first conduit. As shown
in FIG. 5D, a first conduit 200 (or stent) is placed within the
channel 112. FIG. 5D illustrates a second conduit 201 advanced
towards the first conduit 200. FIG. 5E illustrates the second
conduit 201 deployed within the first conduit 200. The second
conduit 201 may have additional properties that permit the channel
to remain patent. For example, the second conduit 201 my have a
tissue barrier as discussed above, or other construction that
generates an aggressive healing response within the lung.
Therefore, the first conduit 200, being more conducive to
implantation, will serve to anchor both conduits 200, 201 as the
tissue either does not grow, or it grows around the outer conduit
200. The second conduit, for example, may have a tissue barrier
placed thereon. Once the second conduit 201 is deployed within the
first conduit 200, the tissue barrier of the second conduit 201
will prevent tissue from growing through the stent structure. It
should be noted that the structure of a conduit within a conduit
may be incorporated into a single composite structure.
In use, the conduit 200 is deployed with the distal side towards
the parenchymal tissue 460 while the proximal side remains adjacent
or in the airway 450. Of course, where the proximal and distal
extension members are identical, the conduit may be deployed with
either side towards the parenchymal tissue.
FIGS. 6A-6B illustrate another example of deploying a conduit 500
in a channel 510 (or opening) created in a tissue wall 520.
Referring to FIG. 6A, a delivery tool 530 carrying a deployable
conduit 500 is inserted into the channel 510. The delivery tool 530
is extended straight from an access catheter 540 such that the
delivery tool forms an angle .beta. with the tissue wall 520. It is
to be understood that while the tissue wall of airway 522 is shown
as being thin and well defined, the present invention may be
utilized to maintain the patency of channels and openings which
have less well defined boundaries. The delivery tool is further
manipulated until the conduit is properly positioned which is
determined by, for example, observing the position of a
visualization mark 552 on the conduit relative to the opening of
the channel 510.
FIG. 6B illustrates enlarging and securing the conduit in the
channel using an expandable member or balloon 560. The balloon 560
may be radially expanded using fluid (gas or liquid) pressure to
deploy the conduit 500. The balloon may have a cylindrical shape
(or another shape such as an hourglass shape) when expanded to 1.)
expand the center section and 2.) deflect the proximal and distal
sections of the conduit such that the conduit is secured to the
tissue wall 520. During this deployment step, the tissue wall 520
may distort or bend to some degree but when the delivery tool is
removed, the elasticity of the tissue tends to return the tissue
wall to its initial shape. Accordingly, the conduits disclosed
herein may be deployed either perpendicular to (or
non-perpendicular to) the tissue wall.
FIG. 7A illustrates another variation of deploying a conduit 200
into an opening 112. In some variations of the invention, prior to
deployment of the conduit 200, the channel 112 may have a diameter
or size that may require an additional dilation or expansion of the
channel 112 for proper deployment of the conduit 200. For example,
the channel 112 may be created by a piercing member, as described
above, where the channel 112 nearly closes upon removal of the
piercing member. However, the devices and method described herein
are not limited to channels 112 of any particular size. The
channels may in fact be larger than a diameter of the conduit 200
in its un-deployed state.
In any case, after creation of the channel 112 the surgeon may
advance a balloon catheter 630 containing a conduit 200 towards the
site of the opening 112. The variation of the balloon catheter 630
depicted in the figure also includes a guide body 632. Because the
opening 112 may be difficult to locate, the guide body 632 may
serve various functions to assist in locating the opening 112 and
placing the conduit 200. For example, as shown in FIG. 7A, the
guide body 632 may have a rounded front surface. This allows
probing of the catheter 630 against the airway 100 wall to more
easily locate the opening 112. The rounded surface of the guide
body 632 will not drag on the airway tissue.
As shown in FIG. 7B, once inserted into the opening 112, the guide
body 632 provides an additional function of temporarily anchoring
the device 630 within the opening 112. The ability to temporarily
anchor the device 630 into the opening 112 may be desirable due to
the natural tidal motion of the lung during breathing. The
increased surface area of the guide body 632 requires increased
resistance upon remove the guide body 632 from the opening 112.
Such a feature lessens the occurrence of unintended removal of the
device from the site as the lung tissue moves. As shown in FIG. 7B,
after insertion into the airway 100 wall, a portion of the guide
body 632 serves as a resistance surface to provide the temporary
anchoring function. Additional variations of the guide body 632 are
shown below.
FIGS. 8A-8F illustrate additional variations of guide bodies 632
for use with the present invention. As shown, the guide body 632 is
located on the distal end of the balloon catheter 630. The guide
body 632 will have a front surface 634 that is preferably smooth
such that it can easily be moved over the airway wall. Proximal to
the front surface 634, the guide body 632 will have at least one
resistance surface 636 which is defined as an area that causes
increased resistance upon removal of the guide body 634 from the
airway wall. As shown, the resistance surface 636 will be adjacent
to an area of reduced diameter 638 to which allows the guide body
632 to nest within the opening 112 in the airway wall. The guide
body 632 may have any number of shapes as shown in the figures.
FIG. 8F illustrates another variation of a guide body 632 having a
resistance surface 636 which comprises an area of increased surface
roughness such that the surface will drag upon the airway wall or
tissue surrounding the channel 112. Such a feature may be combined
with the variations of the guide members provided above.
The balloon catheters 630 of the present invention may include a
dilating member between the guide body 632 and balloon 614. In the
variation shown in FIG. 8A, the dilating member comprises a tapered
section 640. However, the invention is not limited as such. For
example, the dilating member may comprise a second inflatable
balloon, or other expanding device. The dilating members may also
be retractable within the elongate shaft.
FIGS. 9A and 9B depict cross sections of examples of a balloon
catheter 630 having a guide body 632 that includes a lumen 642
which terminates at a surface of the guide body 632. The lumen 642
may be used for suction, irrigation, or deliver bio-active
substances, etc. The catheter 630 may also have an additional
lumens 646, 646, 648 as shown, for inflation of the balloon 614 and
for additional suction 644, and for communication with the guide
body lumen 642. As shown in FIG. 8B, the lumen may also be used to
advance a piercing member 604 to the airway wall to create the
channel 112.
Any of the balloons described herein may be distensible balloons
(e.g., they assume a predetermined shape upon expansion) or elastic
balloons (e.g., simply expand). Use of a distensible balloon
permits control in dilating the opening 112 or placement of the
conduit.
Delivery of Medications/Substances to Parenchymal Tissue
In an additional variation, a medical practitioner may create a
channel to delivery substances such as bioactive agents,
medications, therapeutic substances, or other such materials
through the airway wall and directly to the parenchymal tissue of
the lung.
In such a case, the practitioner engages many of the steps outlined
above such as identifying regions of having severe occurrences of
trapped gas or tissue destruction. However, the methods and channel
creation techniques described herein may also be suitable for a
variety of other disease states affiliated with the lung
(especially cancer and treatment of tumors or other growths). In
the latter cases, an x-ray, ultrasound, Doppler, acoustic, MRI,
PET, computed tomography (CT) scans and/or other non-invasive
imaging technique may be employed to locate the region of diseased
tissue (such as a tumor). In some cases, if the channel is created
solely for the purpose of delivering a substance, then the channel
patency techniques described herein may no longer be applicable.
Instead, after delivery of the substance, the medical practitioner
may desire closure of the channel.
Once the practitioner identifies a region for creation of the
channel, the practitioner may then search for a safe location to
penetrate the airway wall (such as using the blood vessel detection
techniques described above.
After finding a suitable location, the practitioner creates the
opening or channel. Again, any technique described herein may be
used to create the channel. However, FIG. 10A illustrates an
example in which a substance may be delivered during creation of
the channel. In this example, a similar balloon catheter 606 as
described above may have a piercing member 604 that penetrates the
airway wall 450. Once through, the practitioner may inject the
desired substance into parenchymal tissue 460. Although the
illustration shows the piercing member 604 as extending slightly
past the airway wall 450, variations of the method include
delivering a substance to any location beyond the wall.
FIG. 10B illustrates another variation of the method. As shown, a
substance may be delivered through an existing channel/opening 112.
While method may include delivering the substance through a opening
112 with or without an implant 200. In this variation, the channel
112 also includes an implant 200 within the opening 112 with the
substance being delivered through the implant 200. Use of an
implant 200 may be desirable in those cases where trapped gasses
must be evacuate as well as those cases where repeat treatment of a
site is planned (e.g., tumor treatment). In addition, the implant
200 may be removed from the channel 112 to either promote or
inhibit healing depending on the desired benefit. Naturally, this
treatment may be performed in more than one location in the lung,
depending on the areas of intended treatment and/or diseased
tissue. As noted above, the existing channel/opening 112 can be
created such that patency of the existing surgically created
opening is extended beyond at least creation of the surgically
created opening.
The substances that may be delivered as described above may include
any of the substances described herein. In addition, examples of
bioactive substances include, but are not limited to,
antimetabolites, antithrobotics, anticoagulants, antiplatelet
agents, thorombolytics, antiproliferatives, antinflammatories,
agents that inhibit hyperplasia and in particular restenosis,
smooth muscle cell inhibitors, growth factors, growth factor
inhibitors, cell adhesion inhibitors, cell adhesion promoters and
drugs that may enhance the formation of healthy neointimal tissue,
including endothelial cell regeneration. The positive action may
come from inhibiting particular cells (e.g., smooth muscle cells)
or tissue formation (e.g., fibromuscular tissue) while encouraging
different cell migration (e.g., endothelium, epithelium) and tissue
formation (neointimal tissue).
Still other bioactive agents include but are not limited to
analgesics, anticonvulsives, anti-infectives (e.g., antibiotics,
antimicrobials), antineoplastics, H2 antagonists (Histamine 2
antagonists), steroids, non-steroidal anti-inflammatories,
hormones, immunomodulators, mast cell stabilizers, nucleoside
analogues, respiratory agents, antihypertensives, antihistamines,
ACE inhibitors, cell growth factors, nerve growth factors,
anti-angiogenic agents or angiogenesis inhibitors (e.g.,
endostatins or angiostatins), tissue irritants (e.g., a compound
comprising talc), poisons (e.g., arsenic), cytotoxic agents (e.g.,
a compound that can cause cell death), various metals (silver,
aluminum, zinc, platinum, arsenic, etc.), epithelial growth factors
or a combination of any of the agents disclosed herein.
Examples of agents include pyrolitic carbon,
titanium-nitride-oxide, taxanes, fibrinogen, collagen, thrombin,
phosphorylcholine, heparin, rapamycin, radioactive 188Re and 32P,
silver nitrate, dactinomycin, sirolimus, everolimus, Abt-578,
tacrolimus, camptothecin, etoposide, vincristine, mitomycin,
fluorouracil, or cell adhesion peptides. Taxanes include, for
example, paclitaxel, 10-deacetyltaxol, 7-epi-10-deacetyltaxol,
7-xylosyl-10-deacetyltaxol, 7-epi-taxol, cephalomannine, baccatin
III, baccatin V, 10-deacetylbaccatin III, 7-epi-10-deacetylbaccatin
III, docetaxel.
In addition, the substances may be selected to induce a biologic
lung volume reduction such as by using a talc compound, lung
irritant, or fibrin hyrogels containing fibroblast growth factor-1.
The use of such compounds may be found in: U.S. patent application
Ser. No. 09/590,790, filed Jun. 8, 2000 entitled MINIMALLY INVASIVE
LUNG VOLUME REDUCTION ASSEMBLY AND METHOD; U.S. patent application
Ser. No. 10/679,065 filed Oct. 3, 2003 entitled MINIMALLY INVASIVE
LUNG VOLUME REDUCTION ASSEMBLY AND METHOD; and FIBROBLASTS GROWTH
FACTOR-1 THERAPY FOR ADVANCED EMPHYSEMA--A NEW TISSUE ENGINEERING
APPROACH FOR ACHIVEING LUNG VOLUME REDUCTION to Ingenito et al. J.
Bronchol, Vol. 1, 3 Jul. 2006.
All publications, patent applications, patents, and other
references mentioned herein are incorporated by reference in their
entirety. To the extent there is a conflict in a meaning of a term,
or otherwise, the present application will control. Although the
foregoing invention has been described in some detail by way of
illustration and example for purposes of clarity of understanding,
it will be readily apparent to those of ordinary skill in the art
in light of the teachings of this invention that certain changes
and modifications may be made thereto without departing from the
spirit or scope of the appended claims. It is also contemplated
that combinations of the above described embodiments/variations or
combinations of the specific aspects of the above described
embodiments/variations are within the scope of this disclosure.
EXAMPLE
Implant
Implants comprising stainless steel mesh frame fully encapsulated
with a composition comprising silicone (as described below) and
paclitaxel were implanted in several canine models. Visual
observation indicated that, on average, the passage through the
implants of the present invention remained unobstructed and were
associated with significantly reduced fibrotic and inflammatory
responses, in canine models, at a considerably higher rate than an
implant without any drug adjunct or coronary drug eluting stents
(as shown in FIG. 12).
The composition comprised approximately a 9% paclitaxel to silicone
ratio with approximately 400 micrograms of paclitaxel per implant.
Measurements found that approximately 30% of the paclitaxel
released after 60 days. In general, for implants with the
paclitaxel/silicone composition, observations of chronic
inflammation, epithelial metaplasia and fibrosis were all very
mild.
For paclitaxel as the bioactive substance, polymers with solubility
parameters between 5-25 (MPa)^1/2 were believed to provide
sufficient elution rates. The polymer used in the example device
has good diffusivity for lipophilic drug (such as paclitaxel)
because the side methyl group on the silicone may be substituted
with more lipophilic hydrocarbon molecules containing vinyl group
or groups in addition polymerization by platinum catalyst.
The composition for the example may be as follow: polymer part:
polydimethylsiloxane, vinyldimethyl terminated, any viscosity;
and/or polydimethylsiloxane, vinylmonomethyl terminated, any
viscosity. The cross-linker part: polydimethylsiloxane, any
viscosity; and or polymonomethylsiloxane, any viscosity. Platinum
catalyst part and/or cross-linker part: platinum; and/or
platinum-divinyltetramethyldisiloxane complex in xylene, 2-3% Pt;
and/or platinum-divinyltetramethyldisiloxane complex in vinyl
terminated polydimethylsiloxane, 2-3% Pt; and/or
platinum-divinyltetramethyldisiloxane complex in vinyl terminated
polydimethylsiloxane, .about.1% Pt;
platinum-Cyclovinylmethylsiloxane complex, 2-3% Pt in cyclic vinyl
methyl siloxane.
These components may be combined in different ratios to make the
polymer. The hydrocarbon side chain off the silicone back bone
makes this polymer system unique and may result in a
"zero-order"-like release profile. The amount of vinyl siloxane
cross-linker may determine the rate of the drug release and
diffusivity of the polymer to the drug. There are other types of
polydimethylsiloxanes such as: trimethylsiloxy terminated
polydimethylsiloxane in various viscosities, (48-96%) dimethyl
(4-52%) diphenylsiloxane copolymer in various viscosities,
dimethylsiloxane-ethylene oxide copolymer, dimethyl
diphenylsiloxane copolymer, polymethylhydrosiloxane, trimethylsilyl
terminated at various viscosities, (30-55%) methyldro-(45-70%)
dimethylsiloxane copolymer at various viscosities,
polymethylphenylsiloxane, polydimethylsiloxane silanol terminated
at various viscosities, polydimethylsiloxane aminopropyldimethyl
terminated at various viscosities. For paclitaxel a release profile
was found to be acceptable with a polymer system consisting of
polydimethylsiloxane vinyl terminated at various viscosity and a
range of platinum-mono, di, tri and/or tetramethyldisiloxane
complex.
* * * * *
References